Three-dimensional phase-contrast magnetic resonance imaging for the detention of a small communicating defect in a patient with a spinal extradural arachnoid cyst: illustrative case.

BACKGROUND: Spinal extradural arachnoid cysts are thought to be pouches that communicate with the intraspinal subarachnoid space through a dural defect. The treatment for these cysts is resection of the cyst wall followed by obliteration of the communicating defect, which is often elusive. OBSERVATIONS: The authors report the case of a 22-year-old man with an extradural arachnoid cyst with claudication and progressive motor weakness. Regular magnetic resonance imaging (MRI) and computed tomography did not reveal the location of the defect in the cyst. However, three-dimensional (3D) phase-contrast MRI clearly indicated the location of the defect and the flow of cerebrospinal fluid into the cyst. These findings allowed the authors to perform the least invasive surgery; the patient recovered motor function and could walk more smoothly. LESSONS: 3D phase-contrast MRI can reveal a subtle dural defect in patients with spinal extradural arachnoid cysts.

Spinous Process-Splitting Laminectomy Approach for Tumor Excision at Conus Medullaris or Cauda Equina Level Results in Satisfactory Clinical Outcomes Without Affecting Global Spinal Sagittal Alignment.

STUDY DESIGN: Retrospective comparative study. OBJECTIVES: The present study investigated radiographical changes in global spinal sagittal alignment (GSSA) and clinical outcomes following tumor resection using spinous process-splitting laminectomy (SPSL) approach without fixation in patients with conus medullaris (CM) or cauda equina (CE) tumor. METHODS: Forty-one patients with CM or CE tumor (19 males, 22 females, mean age at surgery of 52.9 ± 13.0 years) were included in this study. The variations of outcome variables were analyzed in various GSSA profiles using radiographic outcomes. The clinical outcomes were assessed using Japan Orthopaedic Association (JOA) score and JOA back pain evaluation questionnaire (JOABPEQ). RESULTS: In all cases, the various GSSA parameters (sagittal vertical axis, C2-7 lordosis, T1 slope, thoracic kyphosis, T10-L2 kyphosis, lumbar lordosis [LL; upper, middle, and lower], sacral slope, pelvic incidence, and pelvic tilt) did not significantly change in the 2-years postoperative period. Moreover, age at surgery, the number of resected laminae, preoperative T12-L2 kyphosis, or LL did not affect the postoperative changes in T12-L2 kyphosis or LL, and had no statistically significant correlation among them. The scores of each postoperative JOA domain and the Visual Analogue Scale included in the JOABPEQ were significantly improved. There was no statistical significant group difference in each sagittal profile or clinical outcomes between CM and CE groups postoperatively. CONCLUSIONS: Tumor resection using SPSL approach did not affected the various GSSA parameters examined and resulted in satisfactory clinical outcomes, indicating that SPSL approach is a suitable surgical technique for patients with CM or CE tumor.

Clinical Characteristics of Patients with Ossification of the Posterior Longitudinal Ligament and a High OP Index: A Multicenter Cross-Sectional Study (JOSL Study).

BACKGROUND: The purpose of this study was to clarify the clinical features of ossification of the posterior longitudinal ligament (OPLL) and extreme ossification at multiple sites. METHODS: This prospective study involved patients with a diagnosis of cervical OPLL at 16 institutions in Japan. Patient-reported outcome measures, including responses on the Japanese Orthopaedic Association (JOA) Cervical Myelopathy Evaluation Questionnaire (JOA-CMEQ), JOA Back Pain Evaluation Questionnaire (JOA-BPEQ), and visual analog scale pain score, were collected to investigate clinical status. In each patient, the sum of the levels at which OPLL was located (OP index) was evaluated on whole-spine computed tomography, along with ossification of other spinal ligaments including the anterior longitudinal ligament (OALL), ligament flavum (OLF), supra- and intraspinous ligaments (SSL), and diffuse idiopathic skeletal hyperostosis (DISH). The distribution of OP index values in the study population was investigated, and the clinical and radiologic characteristics of patients in the top 10% were assessed. RESULTS: In total, 236 patients (163 male, 73 female; mean age 63.5 years) were enrolled. Twenty-five patients with OP index ≥ 17 were categorized into a high OP index group and the remainder into a moderate/low OP index group. There were significantly more women in the high OP index group. Patients in the high OP index group also had significantly poorer scores for lower extremity function and quality of life on the JOA-CMEQ and in each domain but not for body pain on the JOA-BPEQ compared with those in the moderate/low OP index group. Patients in the high OP index group had more OALL in the cervical spine and more OLF and SSL in the thoracic spine. The prevalence of DISH was also significantly higher in the high OP index group. In the high OP index group, interestingly, OPLL was likely to be present adjacent to DISH in the cervicothoracic and thoracolumbar spine, especially in men, and often coexisted with DISH in the thoracic spine in women. CONCLUSION: This prospective cohort registry study is the first to demonstrate the clinical and radiologic features of patients with OPLL and a high OP index. In this study, patients with a high OP index had poorer physical function in the lumbar spine and lower extremities and were also predisposed to extreme ossification of spinal ligaments other than the OPLL.

The characteristics of the young patients with cervical ossification of the posterior longitudinal ligament of the spine: A multicenter cross-sectional study.

BACKGROUND: Ossification of the posterior longitudinal ligament of the spine (OPLL) is characterized by heterotopic bone formation in the posterior longitudinal ligament of the spine. Although the patients with OPLL are more common in the 60s and 70s, we know that there are markedly young patients (e.g., early 40s). However, to the best of our knowledge, there is few reports characterize young patients with cervical OPLL in terms of the imaging features, subjective symptoms, and ADL problems. METHODS: This is the multicenter cross-sectional study. Two hundred and thirty-seven Japanese symptomatic patients with cervical OPLL confirmed by standard X-rays collected from 16 institutions belonging to the Japanese Multicenter Research Organization for Ossification of the Spinal Ligament formed by the Japanese Ministry of Health, Labor and Welfare were recruited. Whole spine CT data as well as demographic data such as age, gender, patients-based evaluations, and the 36-item Short Form Health Survey (SF-36) were evaluated. RESULTS: Young group (≦ 45 years old) consisted of 23 patients (8 females and 15 males), accounting for 9.7% of the total. Their characteristics were high body mass index (BMI), significant involvement of trauma in the onset and deterioration of symptoms, and the predominance of thoracic OPLL. The patient-based evaluations did not show a significant difference between the young and non-young groups, or between the genders in the young group except for bodily pain (BP) of SF-36. Female patients in young group had significantly lower BP score of SF-36 than that of male in young group. CONCLUSIONS: Characteristics of young patients with cervical OPLL were high BMI, significant involvement of trauma in the onset and deterioration of symptoms, lower BP score of SF-36 in female, and the predominance of thoracic OPLL.

Risk predictors of perioperative complications for the palliative surgical treatment of spinal metastasis.

BACKGROUND: The complication rate for palliative surgery in spinal metastasis is relatively high, and major complications can impair the patient's activities of daily living. However, surgical indications are determined based primarily on the prognosis of the cancer, with the risk of complications not truly considered. We aimed to identify the risk predictors for perioperative complications in palliative surgery for spinal metastasis. METHODS: A multicentered, retrospective review of 195 consecutive patients with spinal metastasis who underwent palliative surgeries with posterior procedures from 2001 to 2016 was performed. We evaluated the type and incidence of perioperative complications within 14 days after surgery. Patients were categorized into either the complication group (C) or no-complication group (NC). Univariate and multivariate analyses were used to identify potential predictors for perioperative complications. RESULTS: Thirty patients (15%) experienced one or more complications within 14 days of surgery. The most frequent complications were surgical site infection (4%) and motor weakness (3%). A history of diabetes mellitus (C; 37%, NC; 9%: p < 0.01) and surgical time over 300 min (C; 27%, NC; 12%: p < 0.05) were significantly associated with complications according to univariate analysis. Increased blood loss and non-ambulatory status were determined to be potential risk factors. Of these factors, multivariate logistic regression revealed that a history of diabetes mellitus (OR: 6.6, p < 0.001) and blood loss over 1 L (OR: 2.7, p < 0.05) were the independent risk factors for perioperative complications. There was no difference in glycated hemoglobin A1c between the diabetes patients with and without perioperative complications. CONCLUSIONS: Diabetes mellitus should be used for the risk stratification of surgical candidates regardless of the treatment status, and strict prevention of bleeding is needed in palliative surgeries with posterior procedures to mitigate the risk of perioperative complications.

Association between Severity of Diffuse Idiopathic Skeletal Hyperostosis and Ossification of Other Spinal Ligaments in Patients with Ossification of the Posterior Longitudinal Ligament.

BACKGROUND: Although diffuse idiopathic skeletal hyperostosis (DISH) is known to coexist with the ossification of spinal ligaments (OSLs), details of the radiographic relationship remain unclear. METHODS: We prospectively collected data of 239 patients with symptomatic cervical ossification of the posterior longitudinal ligament (OPLL) and analyzed the DISH severity on whole-spine computed tomography images, using the following grades: grade 0, no DISH; grade 1, DISH at T3-T10; grade 2, DISH at both T3-T10 and C6-T2 and/or T11-L2; and grade 3, DISH beyond C5 and/or L3. Ossification indices were calculated as the sum of vertebral and intervertebral levels with OSL for each patient. RESULTS: DISH was found in 107 patients (44.8%), 65 (60.7%) of whom had grade 2 DISH. We found significant associations of DISH grade with the indices for cervical OPLL (r = 0.45, p < 0.0001), thoracic ossification of the ligamentum flavum (OLF; r = 0.41, p < 0.0001) and thoracic ossification of the supra/interspinous ligaments (OSIL; r = 0.53, p < 0.0001). DISH grade was also correlated with the index for each OSL in the whole spine (OPLL: r = 0.29, p < 0.0001; OLF: r = 0.40, p < 0.0001; OSIL: r = 0.50, p < 0.0001). CONCLUSION: The DISH grade correlated with the indices of OSL at each high-prevalence level as well as the whole spine.

Associations between Clinical Findings and Severity of Diffuse Idiopathic Skeletal Hyperostosis in Patients with Ossification of the Posterior Longitudinal Ligament.

BACKGROUND: This study investigated how diffuse idiopathic skeletal hyperostosis (DISH) influences clinical characteristics in patients with cervical ossification of the posterior longitudinal ligament (OPLL). Although DISH is considered unlikely to promote neurologic dysfunction, this relationship remains unclear. METHODS: Patient data were prospectively collected from 16 Japanese institutions. In total, 239 patients with cervical OPLL were enrolled who had whole-spine computed tomography images available. The primary outcomes were visual analog scale pain scores and the results of other self-reported clinical questionnaires. Correlations were sought between clinical symptoms and DISH using the following grading system: 1, DISH at T3-T10; 2, DISH at both T3-10 and C6-T2 and/or T11-L2; and 3, DISH beyond the C5 and/or L3 levels. RESULTS: DISH was absent in 132 cases, grade 1 in 23, grade 2 in 65, and grade 3 in 19. There were no significant correlations between DISH grade and clinical scores. However, there was a significant difference in the prevalence of neck pain (but not in back pain or low back pain) among the three grades. Interestingly, DISH localized in the thoracic spine (grade 1) may create overload at the cervical spine and lead to neck pain in patients with cervical OPLL. CONCLUSION: This study is the first prospective multicenter cross-sectional comparison of subjective outcomes in patients with cervical OPLL according to the presence or absence of DISH. The severity of DISH was partially associated with the prevalence of neck pain.

The impact of ossification spread on cervical spine function in patients with ossification of the posterior longitudinal ligament.

Ossification of the posterior longitudinal ligament (OPLL) is a progressive disease. The bridging of ossified lesions to the vertebral body gradually increases, thereby decreasing the mobility of the cervical spine; thus, cervical spine function may decrease over time. However, cervical spine function in patients with cervical OPLL has not been evaluated in large prospective studies. Therefore, we conducted a prospective multicenter study to clarify whether ossification spread can influence cervical spine function and quality of life (QOL) in patients with cervical OPLL. In total, 238 patients (162 men, 76 women; mean age, 63.9 years) were enrolled from 16 institutions. Each patient underwent whole spine computed tomography and was evaluated for cervical spine function and QOL using the Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire (JOACMEQ). In the multivariate regression analysis, a higher neck VAS score and a larger number of bridge formations of OPLL in the whole spine were significant predictors of adverse outcomes related to cervical spine function. This is the first prospective multicenter study to reveal the impact of ossification spread on cervical spine function. These findings are important to understand the natural course of OPLL and can serve as controls when evaluating postoperative cervical spine function.

Associations between Clinical Symptoms and Degree of Ossification in Patients with Cervical Ossification of the Posterior Longitudinal Ligament: A Prospective Multi-Institutional Cross-Sectional Study.

This study aimed to clarify whether ossification predisposition influences clinical symptoms including pain, restriction of activities of daily living, and quality of life in patients with cervical ossification of the posterior longitudinal ligament (OPLL). Cervical ossification predisposition potentially causes neurologic dysfunction, but the relationship between clinical symptoms and radiologic severity of OPLL has not yet been investigated. Data were prospectively collected from 16 institutions across Japan. We enrolled 239 patients with cervical OPLL. The primary outcomes were patient-reported outcomes, including visual analog scale (VAS) pain scores and other questionnaires. Whole-spine computed tomography images were obtained, and correlations were investigated between clinical symptoms and radiologic findings, including the distribution of OPLL, the sum of the levels where OPLL was present (OP-index), and the canal narrowing ratio (CNR) grade. The cervical OP-index was Grade 1 in 113 patients, Grade 2 in 90, and Grade 3 in 36. No significant correlations were found between radiologic outcomes and VAS pain scores. The cervical OP-index was associated with lower extremity function, social dysfunction, and locomotive function. The CNR grade was not correlated with clinical symptoms, but Grade 4 was associated with lower extremity dysfunction. Thickness and extension of ossified lesions may be associated with lower extremity dysfunction in cervical OPLL.

In vivo monitoring of remnant undifferentiated neural cells following human induced pluripotent stem cell-derived neural stem/progenitor cells transplantation.

Transplantation of human-induced pluripotent stem cell-derived neural stem/progenitor cells (hiPSC-NS/PCs) is a promising treatment for a variety of neuropathological conditions. Although previous reports have indicated the effectiveness of hiPSC-NS/PCs transplantation into the injured spinal cord of rodents and nonhuman primates, long-term observation of hiPSC-NS/PCs post-transplantation suggested some "unsafe" differentiation-resistant properties, resulting in disordered overgrowth. These findings suggest that, even if "safe" NS/PCs are transplanted into the human central nervous system (CNS), the dynamics of cellular differentiation of stem cells should be noninvasively tracked to ensure safety. Positron emission tomography (PET) provides molecular-functional information and helps to detect specific disease conditions. The current study was conducted to visualize Nestin (an NS/PC marker)-positive undifferentiated neural cells in the CNS of immune-deficient (nonobese diabetic-severe combined immune-deficient) mice after hiPSC-NS/PCs transplantation with PET, using 18 kDa translocator protein (TSPO) ligands as labels. TSPO was recently found to be expressed in rodent NS/PCs, and its expression decreased with the progression of neuronal differentiation. We hypothesized that TSPO would also be present in hiPSC-NS/PCs and expressed strongly in residual immature neural cells after transplantation. The results showed high levels of TSPO expression in immature hiPSC-NS/PCs-derived cells, and decreased TSPO expression as neural differentiation progressed in vitro. Furthermore, PET with [18 F] FEDAC (a TSPO radioligand) was able to visualize the remnant undifferentiated hiPSC-NS/PCs-derived cells consisting of TSPO and Nestin+ cells in vivo. These findings suggest that PET with [18 F] FEDAC could play a key role in the safe clinical application of CNS repair in regenerative medicine.

The characteristics of the patients with radiologically severe cervical ossification of the posterior longitudinal ligament of the spine: A CT-based multicenter cross-sectional study.

BACKGROUND: Ossification of the posterior longitudinal ligament of the spine (OPLL) is characterized by heterotopic bone formation in the posterior longitudinal ligament of the spine. We know that the size and distribution of the ossified lesions in patients with OPLL are different in each case. However, the characteristics of the patients with radiologically severe cervical OPLL remain unknown. METHODS: The participants of our study were symptomatic patients with cervical OPLL who were diagnosed by standard radiographs of the cervical spine. Whole-spine CT data and demographic data such as age and sex were obtained from 20 institutions belonging to the Japanese Multicenter Research Organization for Ossification of the Spinal Ligament. According to the number of the levels involved by OPLL, we stratified the patients into two subgroups: severe group (S-group) and non-severe group (NS-group) to delineate the characteristics of radiologically severe patients with cervical OPLL. We also evaluated the most compressed level and the degree of occupying ratio of cervical spinal canal by OPLL at the most compressed level. RESULTS: A total of 234 patients with a mean age of 65 years were recruited. The S-group consisted of 48 patients (21%, 12 females and 36 males) and the NS-group consisted of 92 patients (79%, 22 females and 70 males). The mean age of males in the S-group (68 years old) was significantly higher than that of males in the NS-group (64 years old); however there was no significant difference in the mean age in females between the S-group (69 years old) and the NS-group (66 years old). No significant difference of body mass index, ossification of the nuchal ligament-positivity and presence of diabetes mellitus were found between the S- and the NS-group. CONCLUSIONS: It is likely that the manner of extension of cervical OPLL is different between male and female patients.

Co-existence of ossification of the nuchal ligament is associated with severity of ossification in the whole spine in patients with cervical ossification of the posterior longitudinal ligament -A multi-center CT study.

BACKGROUND: Previous studies have shown that patients with cervical ossification of the posterior longitudinal ligament (OPLL) often have co-existing ossification of the nuchal ligament (ONL). However, no studies have focused on ONL and its relevance to the severity of OPLL or ossification of other spinal ligaments, such as anterior longitudinal ligament (OALL), ligamentum flavum (OLF), and supraspinous/interspinous ligament (OSIL). METHODS: In this multicenter study, we investigated ossification of the spinal ligaments in the whole spine computed tomography (CT) images of 233 cervical OPLL patients. The severity of ossification was evaluated using ossification index for each spinal ligament, calculated as the sum of the level of ossification. We compared the severity of ossification in each spinal ligament between patients with ONL and those without ONL. Furthermore, we investigated how the number of segments, where ONL exists, affects the severity of ossification in each spinal ligament. RESULTS: One hundred thirty patients (55.8%) had co-existing ONL in the cervical OPLL patients included in this study. The ONL (+) group included more male and aged patients. The cervical ossification indexes of OPLL and OALL were higher in ONL (+) patients than in ONL (-) patients. The thoracolumbar ossification indexes of OALL and OSIL were also higher in ONL (+) patients. Logistic regression analysis revealed that age, gender and cervical OA-index were independent factors correlating to the existence of ONL. In the cervical spine, both the ossification indexes of OALL and OPLL increased as the levels of ONL increased. Similarly, in the thoracolumbar spine, both the ossification indexes of OALL and OSIL were increased as the levels of cervical ONL increased. In the multiple regression analysis, cervical OA-index and thoracolumbar OSI-index showed significant correlation with the number of ONL levels. CONCLUSIONS: Co-existence of ONL in cervical OPLL patients was associated with the severity of spinal hyperostosis especially in cervical OPLL, OALL, thoracolumbar OALL and OSIL.

Prevalence and Distribution of Diffuse Idiopathic Skeletal Hyperostosis on Whole-spine Computed Tomography in Patients With Cervical Ossification of the Posterior Longitudinal Ligament: A Multicenter Study.

STUDY DESIGN: This was a retrospective multicenter study. OBJECTIVE: To clarify the progression of diffuse idiopathic skeletal hyperostosis (DISH) using whole-spine computed tomography in patients with cervical ossification of the posterior longitudinal ligament (OPLL). SUMMARY OF BACKGROUND DATA: DISH and cervical OPLL frequently coexist, and can cause ankylosing spinal fractures due to biomechanical changes and fragility of the affected vertebrae. The epidemiology and pathophysiology of DISH occurring with cervical OPLL are unclear. MATERIALS AND METHODS: We used whole-spine computed tomography to determine the prevalence of DISH in 234 patients with a diagnosis of cervical OPLL based on plain cervical radiographs. We established a novel system for grading the progression of DISH based on a cluster analysis of the DISH distribution along the spine. We calculated the correlation coefficient between this grading system and patient age. RESULTS: The prevalence of DISH in patients with cervical OPLL was 48.7%. Patients with DISH were significantly older than those who did not have DISH (67.3 vs. 63.4 y; P=0.005). Cluster analysis classified the DISH distribution into 6 regions, based on the levels affected: C2-C5, C3-T1, C6-T5, T3-10, T8-L2, and T12-S1. DISH was observed most frequently at T3-T10. We defined a system for grading DISH progression based on the number of regions involved, from grade 0 to 6. DISH was distributed at T3-T10 in >60% of the grade 1 patients, whereas most patients with DISH at the cervical or lumbar spine were grade 4 or 5. There was a weak but significant correlation between the DISH grade and patient age. CONCLUSIONS: DISH was present in nearly half of the patients with cervical OPLL. DISH was more common in older patients. DISH developed at the thoracic level and progressed into the cervical and/or lumbar spine with age. LEVEL OF EVIDENCE: Level III.

The Amelioration of Pain-Related Behavior in Mice with Chronic Spinal Cord Injury Treated with Neural Stem/Progenitor Cell Transplantation Combined with Treadmill Training.

Progress in regenerative medicine is realizing the possibility of neural regeneration and functional recovery in spinal cord injury (SCI). Recently, rehabilitation has attracted much attention with respect to the synergistic promotion of functional recovery in combination with neural stem/progenitor cell (NS/PC) transplantation, even in the chronic refractory phase of SCI. Nevertheless, sensory disturbance is one of the most prominent sequelae, even though the effects of combination or single therapies have been investigated mostly in the context of motor recovery. To determine how combination therapy with treadmill training (TMT) and NS/PC transplantation affects the manifestation of thermal allodynia and tactile hyperalgesia in chronic phase SCI, four groups of SCI mice were used to assess pain-related behavior and histological changes: combined transplantation and TMT therapy, transplantation only, TMT only, and control groups. Thermal allodynia and coarse touch-pressure hyperalgesia exhibited significant recovery in the combined therapy group in comparison with controls, whereas there were no significant differences with fine touch-pressure hyperalgesia and motor function. Further investigation revealed fewer fibers remaining in the posterior funiculus, which contained the tracts associated with the two modalities showing less recovery; that is, touch-pressure hyperalgesia and motor function. A significant correlation was only observed between these two modalities. Although no remarkable histological recovery was found within the lesion epicenter, changes indicating amelioration of pain were observed in the lumbar enlargement of the combination therapy group. Our results suggest that amelioration of thermal allodynia and tactile hyperalgesia can be brought about by the additive effect of NS/PC transplantation and TMT. The degree of recovery seems dependent on the distribution of damage.

Distribution of ossified spinal lesions in patients with severe ossification of the posterior longitudinal ligament and prediction of ossification at each segment based on the cervical OP index classification: a multicenter study (JOSL CT study).

BACKGROUND: In patients with ossification of the posterior longitudinal ligament (OPLL) in the cervical spine, it is well known that the thoracic ossified lesions often coexist with the cervical lesions and can cause severe myelopathy. However, the prevalence of OPLL at each level of the thoracic and lumbar spinal segments is unknown. The aims of this study were to investigate how often OPLL occurs at each level in the thoracolumbar spine in patients with a radiological diagnosis of cervical OPLL and to identify the spinal levels most likely to develop ossification. METHODS: Data were collected from 20 institutions in Japan. Three hundred and twenty-two patients with a diagnosis of cervical OPLL were included. The OPLL index (OP index), defined as the sum of the vertebral body and intervertebral disc levels where OPLL is present, was used to determine disease severity. An OP index ≥20 was defined as severe OPLL. The prevalence of OPLL at each level of the thoracic and lumbar spinal segments was calculated. RESULTS: Women were more likely to have ossified lesions in the thoracolumbar spine than men. Severe OPLL was significantly more common in women than in men (20% vs. 4.5%). For thoracic vertebral OPLL, the most frequently affected was the T1 segment in both men and women, followed by the T1/2 and T3/4 intervertebral levels in men and women, respectively. Ossified lesions were frequently seen at the intervertebral and vertebral levels around the cervicothoracic and thoracolumbar junctions in men with severe OPLL, whereas OPLL was more diffusely distributed in the thoracic spine in women with severe OPLL. CONCLUSION: Thoracolumbar OPLL occurred most often at T1 in men and at T3/4 in women. In severe OPLL cases, although ossified lesions were frequently seen at the intervertebral and vertebral levels around the cervicothoracic and thoracolumbar junctions in men, OPLL could be observed more diffusely in the thoracic spine in women.

Enteric Glial Dysfunction Evoked by Apolipoprotein E Deficiency Contributes to Delayed Gastric Emptying.

BACKGROUND AND AIM: Diabetes is the main cause of gastroparesis accompanying decreased neuronal nitric oxide synthase (nNOS) in myenteric ganglia of the stomach. Decreased nNOS expression in the stomach also results from defects in apolipoprotein E (ApoE), which is secreted by astrocytes and has neuroprotective effects on the central nervous system. However, the roles of ApoE and enteric glial cells on gastric motility are uncertain. In this study, ApoE and enteric glial cell alterations in gastroparesis were investigated. METHODS: Type 2 diabetic (db/db) mice and ApoE-knockout mice were analyzed. Gastric emptying was measured using the 13C acetic acid breath test. Expression levels of the pan-neuronal marker, protein gene product 9.5 (PGP 9.5), and glial marker, glial fibrillary acidic protein (GFAP) were examined by immunohistochemistry. Neural stem cells (NSCs) were injected into the gastric antral wall of ApoE-knockout mice. RESULTS: Delayed gastric emptying was observed in 27% of db/db mice with significant decreases in serum ApoE levels and GFAP expression in the gastric antrum. Gastric emptying was also delayed in ApoE-knockout mice, with a significant decrease in GFAP expression, but no change in PGP 9.5 expression. Transplantation of NSCs improved gastric emptying in ApoE-knockout mice through supplementation of GFAP-positive cells. CONCLUSIONS: Our results suggest that decreased enteric glial cells in ApoE-knockout mice are crucial for development of delayed gastric emptying, and NSC transplantation is effective in restoring myenteric ganglia and gastric motility.

Discography aids definitive diagnosis of posterior epidural migration of lumbar disc fragments: case report and literature review.

BACKGROUND: Posterior epidural migration of lumbar disc fragments (PEMLDF) is extremely rare. It is often confused with other posterior lesions and is usually diagnosed intraoperatively. We here describe the use of preoperative discography in the diagnosis of PEMLDF. CASE PRESENTATION: A 78-year-old man presented with acute low back pain, gait disturbance, and paresthesia in both legs. Magnetic resonance imaging showed a mass located posteriorly and laterally to the left aspect of the dural sac at the L3 level. The initial diagnosis indicated PEMLDF, malignancy, spontaneous hematoma, or epidural abscess. L3/4 discography clearly showed leakage of the contrast medium into the posterior dural space, indicating PEMLDF. The lesion was identified intraoperatively as a herniated-disc fragment, consistent with the preoperative discography. CONCLUSION: PEMDLF is difficult to diagnose preoperatively. Discography is useful for the definitive diagnosis of PEMDLF prior to surgery.

Evaluation of the immunogenicity of human iPS cell-derived neural stem/progenitor cells in vitro.

To achieve the goal of a first-in-human trial for human induced pluripotent stem cell (hiPSC)-based transplantation for the treatment of various diseases, allogeneic human leukocyte antigen (HLA)-matched hiPSC cell banks represent a realistic tool from the perspective of quality control and cost performance. Furthermore, considering the limited therapeutic time-window for acute injuries, including neurotraumatic injuries, an iPS cell bank is of potential interest. However, due to the relatively immunoprivileged environment of the central nervous system, it is unclear whether HLA matching is required in hiPSC-derived neural stem/progenitor cell (hiPSC-NS/PC) transplantation for the treatment of neurodegenerative diseases and neurotraumatic injuries. In this study, we evaluated the significance of HLA matching in hiPSC-NS/PC transplantation by performing modified mixed lymphocyte reaction (MLR) assays with hiPSC-NS/PCs. Compared to fetus-derived NS/PCs, the expression levels of human leukocyte antigen-antigen D related (HLA-DR) and co-stimulatory molecules on hiPSC-NS/PCs were significantly low, even with the addition of tumor necrosis factor-α (TNFα) and/or interferon-γ (IFNγ) to mimic the inflammatory environment surrounding transplanted hiPSC-NS/PCs in injured tissues. Interestingly, both the allogeneic HLA-matched and the HLA-mismatched responses were similarly low in the modified MLR assay. Furthermore, the autologous response was also similar to the allogeneic response. hiPSC-NS/PCs suppressed the proliferative responses of allogeneic HLA-mismatched peripheral blood mononuclear cells (PBMCs) in a dose-dependent manner. Thus, the low antigen-presenting function and immunosuppressive effects of hiPSC-NS/PCs result in a depressed immune response, even in an allogeneic HLA-mismatched setting. It is crucial to verify whether these in vitro results are reproducible in a clinical setting.

Prevalence and distribution of ossification of the supra/interspinous ligaments in symptomatic patients with cervical ossification of the posterior longitudinal ligament of the spine: a CT-based multicenter cross-sectional study.

BACKGROUND: Supra/interspinous ligaments connect adjacent spinous processes and act as a stabilizer of the spine. As with other spinal ligaments, it can become ossified. However, few report have discussed ossification supra/interspinous ligaments (OSIL), so its epidemiology remains unknown. We therefore aimed to investigate the prevalence and distribution of OSIL in symptomatic patients with cervical ossification of the posterior longitudinal ligament (OPLL). METHODS: The participants of our study were symptomatic patients with cervical OPLL who were diagnosed by standard radiographs of the cervical spine. The whole spine CT data as well as clinical parameters such as age and sex were obtained from 20 institutions belong to the Japanese Multicenter Research Organization for Ossification of the Spinal Ligament (JOSL). The prevalence and distribution of OSIL and the association between OSIL and clinical parameters were reviewed. The sum of the levels involved by OPLL (OP-index) and OSIL (OSI-index) as well as the prevalence of ossification of the nuchal ligament (ONL) were also investigated. RESULTS: A total of 234 patients with a mean age of 65 years was recruited. The CT-based evidence of OSIL was noted in 68 (54 males and 14 females) patients (29%). The distribution of OSIL showed a significant thoracic preponderance. In OSIL-positive patients, single-level involvement was noted in 19 cases (28%), whereas 49 cases (72%) presented multi-level involvement. We found a significant positive correlation between the OP-index grade and OSI-index. ONL was noted at a significantly higher rate in OSIL-positive patients compared to negative patients. CONCLUSIONS: The prevalence of OSIL in symptomatic patients with cervical OPLL was 29%. The distribution of OSIL showed a significant thoracic preponderance.

Functional Recovery from Neural Stem/Progenitor Cell Transplantation Combined with Treadmill Training in Mice with Chronic Spinal Cord Injury.

Most studies targeting chronic spinal cord injury (SCI) have concluded that neural stem/progenitor cell (NS/PC) transplantation exerts only a subclinical recovery; this in contrast to its remarkable effect on acute and subacute SCI. To determine whether the addition of rehabilitative intervention enhances the effect of NS/PC transplantation for chronic SCI, we used thoracic SCI mouse models to compare manifestations secondary to both transplantation and treadmill training, and the two therapies combined, with a control group. Significant locomotor recovery in comparison with the control group was only achieved in the combined therapy group. Further investigation revealed that NS/PC transplantation improved spinal conductivity and central pattern generator activity, and that treadmill training promoted the appropriate inhibitory motor control. The combined therapy enhanced these independent effects of each single therapy, and facilitated neuronal differentiation of transplanted cells and maturation of central pattern generator activity synergistically. Our data suggest that rehabilitative treatment represents a therapeutic option for locomotor recovery after NS/PC transplantation, even in chronic SCI.